We will use the awake rat to investigate whether ventilation follows the changes in acid-base balance, central respiratory drive, and lung mechanics during prolonged hypercapnia. Awake animals will be continuously exposed to 10 percent CO2 for up to three weeks. Minute ventilation, lung mechanics, central respiratory activity, thoracic gas volume, and acid-base parameters will be measured during the last five minutes of a certain period of 10 percent CO2 breathing. The same measurements will also be performed during the last five minutes of a 20-minute breathing of 5 percent CO2 and then of room air. Similar determinations with the same sequence will be done in paired control rats breathing 10 percent, 5 percent CO2 and room air for 20 minutes. We will use these data to analyze factors contributing to the change in respiration during different time periods of hypercapnia. In order to look into the effect of hypercapnia-hypoxia on ventilation during moderate long time exposure, we plan to do above measurements in the awake rat breathing 10 percent CO2-10 percent O2. To determine the site of action of CO2, we will perform studies in awake rats with denervated peripheral chemoreceptors, i.e. with cut carotid sinus nerves, during prolonged hypercapnic exposure.